title: The C. elegans P4-ATPase TAT-1 regulates lysosome biogenesis and endocytosis.
abstract: P-type adenosine triphosphatases (ATPases) of the Drs2p family (P4-ATPases) are multipass transmembrane proteins required to generate and maintain phospholipid asymmetry in membrane bilayers. In Saccharomyces cerevisiae, several members of this family control distinct transport events within the endosomal and secretory pathways. Comparatively, little is known about the functions of P4-ATPases in multicellular organisms. In this study, we analyzed the role of the Caenorhabditis elegans Drs2p homologue transbilayer amphipath transporter (TAT)-1 in intracellular trafficking. tat-1 is expressed in many tissues including the intestine, the epidermis and the nervous system. In intestinal cells, tat-1 loss-of-function mutants accumulate large vacuoles of mixed endolysosomal identity positive for the lysosomal protein LMP-1. In addition, they lack the same class of storage granules as lmp-1 mutants, suggesting that part of the tat-1 phenotype might result from LMP-1 sequestration in an aberrant compartment. Epidermal cells mutant for tat-1 contain acidified giant hybrid multivesicular bodies probably corresponding to endolysosomal intermediate compartments or deficient lysosomes. Finally, TAT-1 is required for yolk uptake in oocytes and an early step of fluid-phase endocytosis in the intestine. Hence, TAT-1 is required at multiple steps of the endolysosomal pathway, at least in part by ensuring proper trafficking of cell-specific effector proteins.
authors.affiliation: ENS, Biologie cellulaire de la synapse, INSERM U789, Paris, France.
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Ruaud
authors.forename: Lars
authors.initials: L
authors.lastname: Nilsson
authors.forename: Fabrice
authors.initials: F
authors.lastname: Richard
authors.forename: Morten Krog
authors.initials: MK
authors.lastname: Larsen
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bessereau
authors.forename: Simon
authors.initials: S
authors.lastname: Tuck
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D001678:Organelle Biogenesis; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D021381:Protein Transport; D013997:Time Factors; D014617:Vacuoles / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D049294:Phospholipid Transfer Proteins; D000251:Adenosine Triphosphatases; C522446:TAT-1 protein, C elegans